Ureidoalkylphosphonic acids

ABSTRACT

R is alkyl or haloalkyl of one to five carbon atoms, R&#39;&#39; is R, OH or OR, R&#39;&#39;&#39;&#39; is hydrogen, alkyl or aryl of one to 15 carbon atoms, R&#39;&#39;&#39;&#39;&#39;&#39; is alkyl, alkenyl, aryl, chloroaryl or bromoaryl groups of one to 15 carbon atoms, and Z is CO, CS or SO2. The phosphorus compounds have utility as fire retardants and as biologically active materials.   The present invention relates to new nitrogen-containing organophosphorus compounds having alkoxy or alkyl substituents bonded to phosphorus in ester or phosphine oxide structures and to organophosphorus acids that can be produced by hydrolysis of the esters.

Birum United States Patent. 1 1

[52] US. Cl. 260/502.5; 71/86; 71/87; 260/45.9 R; 260/92.8; 260/606.5 P;

[51] Int. Cl. C07F 9/38 [58] Field of Search 260/502.5

[56] References Cited UNITED STATES PATENTS 2,304,156 12/1942 Englemann et a1. 260/502.5 2,579,810 12/1951 Fields 260/502.5 2,635,112 4/1953 Fields '260/5025 2,953,595 9/1960 Rauhut et al. 260/502.5 3,121,731 2/1964 Quesnel et a1. 260/502.5 3,184,496 5/1965 Baranauckas et al........ 260/502.4 R 3,202,692 8/1965 Wei] et a1 2613/5024 R 3,223,514 12/1965 Gradsten .."260/502.5 3,322,716 5/1967 Klein 61: a1. 260/502.5

3,322,863 5/1967 Raboum et a1. 260/502.5

3,455,675 7/1969 lrani 1 2'60/5025 3,763,281 10/1973 Wei] 260/932 [4 1 Nov. 18,- 1975 a Primary Examiner-Joseph Evans 57 ABSTRACT The present invention relates to new nitrogencontaining organophosphorus Compounds having alk oxy or .alkyl substituents bonded to phosphorus in ester or phosphine oxide structures and to organo phosphorus acids that can be produced by hydrolysis of the esters.

R is alkyl, alkenyl, aryl, chloroaryl or bromoaryl I groups of one to 15 carbon atoms, and

Z is CO, CS or S0 The phosphorus compounds have utility fire retardants and as biologically active materials.

4 Claims, N0 Drawings UREIDOALKYLPHOSPHONIC ACIDS The present invention relates to new nitrogen-containing organophosphorus compounds having alkoxy or alkyl substituents bonded to phosphorus in ester or phosphine oxide structures. While the esters or phosphine oxides are characterized by' alkoxy or alkyl groups bonded to phosphorus, the remainder of the molecule may have aryl as well as alkyl substituents. When the products are esters, they can be hydrolized to the corresponding acids.

A new process for the production of such compounds is also a part of the present invention.

The general method for the production of the novel nitrogen-containing organophosphorus compositions, including the formation of acids, is in accordance with the equation shown below:

HOP-CHNHZNR",

where R is alkyl or haloalkyl of one to five carbon atoms,

R is R, OH or OR,

R" is hydrogen, alkyl or aryl of one to 15 carbo atoms,

R' is alkyl, alkenyl, aryl, chloroaryl or bromoaryl groups of one to 15 carbon atoms, and

Z is CO, CS or S A specific compound is:

When both R" radicals of the reactant, H NZNR" are hydrogen, the product can also contain two phosphorus moieties according to the formula,

exemplified by CH; H;

In such cases both the monoand diphosphorus-containing structures are usually obtained if the reactants ROPR and R"'CHO are used in less than two molar proportions relative to the third reactant, H NZNH However, if at least two molar proportions of both R0- 2 PR and R"'CHO are used relative to H NZNH and the temperatures and time employed are sufficient to complete the reaction, the diphosphorus-containing product may be obtained essentially exclusively.

Formation of the compounds of this invention is usually initiated when a mixture of the three reactants is warmed to about C. The reaction is usually complete after 1 hour at l 20C., but warming at lower or higher temperatures is sometimes advantageous. An alternate procedure, which may facilitate control of heat of reaction, is to gradually add the aldehyde reactant to a stirred mixture of the phosphorus ester and urea reactants at reaction temperature, generally from about 70 to C. The use of an inert solvent, for example, toluene, chlorobenzene, and l,2-dichloroethane, maysometimes be beneficial.

When R and R are unsubstituted alkyl radicals, the reaction is generally slow unless acid catalysts are used, particularly boron trifluoride etherate or carboxylic acids such as acetic acid, propionic acid, butyric acid and benzoic acid.

The present invention also includes the free acids of the corresponding esters discussed above. Thus, when the ester is a phosphinate, that is, one R is alkoxy or haloalkoxy, the ester may be hydrolyzed to the corresponding phosphinic acid.

ll l R'T-CHNHZNR"; and R'PCHNHZNHCHFI'R' Ho II! I R!!! RIIIOH If both R radicals are alkoxy or haloalkoxy, the esters are hydrolyzed to phosphonic acids,

(HOhFfHNl-IZNR"; and (HO);PCHNHZNHCHP(OH) III exemplified by In cases where a mixture of monoand diphosphoruscontaining ester products are produced by using less than two molar proportions of (RO) PR' and R"CHO relative to H NZNH it has generally been found that selective hydrolysis of the monophosphorus ester can be accomplished by treating the crude mixture of esters with at least a stoichiometric quantity of water at a temperature in the range of 10 to C. The relatively insoluble monophosphorus acid thus produced can be readily separated from the unhydrolyzed diphosphorus ester by standard techniques such as filtration. The diphosphorus esters can normally be hydrolyzed to the corresponding acids at higher temperatures than needed for the monophosphorus esters, or the hydrolysis can usually be accomplished more readily by the use of dilute aqueous acids such as hydrochloric acid, hy-

drobromic acid, and sulfuric acid.

Specific examples showing the preparation and isolation of representative compounds of the present invention are set forth herewith, but are not limitative of the scope of the invention.

EXAMPLE 1 A 2-liter, four-necked flask equipped with a thermometer, mechanical stirrer, dropping funnel, and dry ice-cooled condenser is swept with nitrogen and charged with 539.0g (2.0 moles) of crude tris(2- chloroethyl) phosphite, 60.0g (1.0 mole) of powdered urea, and one-half of 94.6g (2.15 moles) of freshly distilled acetaldehyde. When this mixture is warmed, refluxing begins at 47C and the temperature is gradually increased to 60 in 25 minutes. The mantle is removed, and the heat of reaction raises the temperature to 82 in 15 minutes. The remainder of the acetaldehyde is then added below the surface of the reaction mixture in l 1 minutes at 6575. Warming at 9095 for 0.5 hr gives a clear, colorless solution: P nmr -27.6 ppm. One pint of 1,2-dichloroethane is added, and the solution is washed five times with 400 ml portions of water and Y then stripped to l10/0.2mm to give 469g (89%) of col- 3 C1, 26.95; N, 5.32; P. 11.77. Found: C, 29.75; H, 5.08;

Cl, 27.00; N, 5.22; P, 11.63.

A solid forms after a portion of the viscous liquid is several times diluted with acetone and finally with ether and the solvent allowed to evaporate each time. Recrystallization twice from acetonitrile-ether gives a white solid: mp 138140; F nmr-27.8 ppm(m); H nmr 8 6.45 (d, 2, J 101-12, NH), 4.1 to 4.8 (m, 10, POCl-l and PCH), 3.5 to 3.9 (m, 8, CICH 1.38 (d of d, 6, J =17 and 7H2, CH ir(1(Br) 2.97(m), 3.33(w), 5.89(s), 6.38(s), 6.83(m), 7.93(s), 8.13(s), 9.2(s), 6.65u (vs); molecular weight (DMF) 516.

Anal. Found: C, 29.97; H, 5.09; Cl, 26.99; N, 5.28; P. 11.71.

EXAMPLE 2 Tetrakis( l-bromo-3-chloro-iso-propyl) (ureylenediethyl)diphosphonate BrCH 0 0 CH Br ll 11 ll CHO PCHNHCNHCHP OCH ClCH H CH CH,C1 2

When a mixture of 548.3g (1.0 mole) of crude tris (l-bromo-3-chloro-iso-propyl) phosphite, 30.0g (0.5 mole) of powdered urea, and 48.4g (1.1 moles) of redistilled acetaldehyde in 300g of 1,2-dich1oroethane is stirred under nitrogen without warming, the temperature increases spontaneously from 24 to 78C in 43 minutes before subsiding. The reaction mixture is then warmed at 85-90 for 0.5 hr, giving a brown solution: P nmr 27.0 ppm(m). Stripping to ll7/O.5mm gives 482g of viscous, red-brown liquid. A 50g portion is twice stirred in ether and the ether allowed to evaporate to give a mixture of solid and red oil. The solid is separated by suction filtration and then recrystallized from acetone to give 16.6g, mp 140 148. Recrystallization of a portion from acetone gives white solid: mp 145148; P nmr-27.1 ppm(m); H nmr 86.30 (d, 2, J 8.5Hz, NH), 4.75 (m, 6,C1-1O and CHN), 3.78 (m, 16, Cl-l Br and CH Cl), 1.42 (d of d, 6, J =18 and 7H2, CH molecular weight (acetone) 898 (calcd 898).

Anal. Calcd for C H BuChN O P z Br, 35.58; C1, 15.79; N, 3.13; P, 6.90. Found: Br, 35.47; Cl, 15.62; N, 2.86; P, 6.74.

EXAMPLE 3 Bis(2-chloroethyl) l'sulfamidobutylphosphonate (CICH CH O )2PCHNHSO NH CH CH CH When a mixture of 0.55 mole of tris(2-chloroethyl) phosphite, 0.50 mole of n-butyraldehyde, and 0.50 mole of sulfamide is warmed to C, a reaction is initiated, and cooling is needed for a few minutes to keep the temperature below 100. The reaction mixture is warmed at 100 for 0.5 hr. and then stripped to at 0.5 mm. The addition of 150 ml. of ether to the residue and cooling causes a solid to separate. This is separated, washed with water, and recrystallized from benzene to give a white solid: mp 8587; P nmr 25.6 ppm.

Anal. Calcd for C H Cl N O PS: C, 26.90; H, 5.36; CI, 19.85; N, 7.84; P, 8.67; S, 8.98. Found: C, 27.14; H, 5.46; C], 20.25; N, 7.99; P, 8.58; S, 9.05.

Similar treatment of equimolar quantities of tris(2- chloroethyl) phosphite, sulfamide, and p-bromophenylacetaldehyde or, in another synthesis, p-trifluoromethyl phenylacetaldehyde, gives bis(2-chloroethyl) l-sulfamido-2-p-bromophenylethylphosphonate and bis( 2-chloroethyl) 1-sulfamido-2-p-trifluromethylphenylethylphosphonate, respectively. Hydrolysis of these phosphonate esters gives the corresponding phosphonic acids.

Freshly distilled propionaldehyde, 58.0g (1.0 mole), is added dropwise in 1 hr to a stirred mixture of 60.0g (1.0 mole) of powdered urea and 269.5g (1.0 mole) of crude tris (2-chloroethyl) phosphite at -112 C. Heat of reaction keeps the temperature at this level without external warming during most of the aldehyde addition. The reaction mixture is warmed for 0.25 hr more, and then it is stripped to 122l2mm, giving a viscous yellow residue,crude bis(2-chloroethyl) l-ureidopropylphosphonate. This is dissolved in 100ml of acetonitrile and 36g (2.0 moles) of water, and the solution is warmed at reflux for 1 hr. A solid forms during warming and is separated by filtration of the warm reaction mixture; and then it is stirred and warmed in more acetonitrile and water, and the mixture is filtered while warm to give 76.2g (42%) of white solid, mp l85l 86 dec. A 5.0-g portion is recrystallized from acetic acid- 011 and Nl;l ),'6.2 (broad, 1, NH), 3.7 (broad, 1, CH), 1.6 and 0.9 (broad, 5,'Cl;l C1j acidity 2.01 equiv/- mole, pK1 2.70, pK 7.30. I

Anal. Calcd for C H N O P: C, 26.38; H, 6.09; N, 15.38; P, 17.01. Found: C, 26.50; H, 6.1 1; N, 15.26; P, 16.99. 4

EXAMPLE 5 [Urylenedi(2-methylpropyl)]diphosphonic acid CH(CH CH(CH=)1 Tetrakis(2-chloroethyl) [ury1enedi(2-methylpropyl] diphosphonate (A) is prepared from tris(2-chloroethyl)phosphite, urea, and iso-butyraldehyde by a procedure similar to that used for the preparation of Example l. When a solution of 11.8g (0.02 mole) of A, mp 146150, and 2.9g (0.16 mole) of distilled H O in 75ml of acetonitrile is warmed at reflux for 7 hr, A is recovered unchanged. The recovered A is then stirred at reflux with 2.9g of distilled H 0 and 1 ml of concentrated hydrochloric acid in 75ml of acetonitrile for 6 hr. A solid, 4.4g (67%), that separates during this warming period is recrystallized from CH C N -H O and then from CH CO HH O to give the white solid product: mp (appears to melt at 215, resolidifies and then remelts at 275-280 with foaming); P nmr (DMSO-d 22.8 ppm(m); 1-1 nmr 88.6(s, 5, go and NH), 6.3 (broad, 1, NH), 3.8 (m, 2, CHP), 2.0 [m, 2, C1;l(CH;,) acidity by potentiometric titration 4.10 equiv/mole, pK 2.71 pK 8.24.

Anal. Calcd for C H N O P C, 32.54; H, 6.68; N, 8.43; P, 18.64. Found: C, 32.64; H, 6.40; N, 8.35; P, 18.51.

EXAMPLE 6 Tetramethyl [urylenedi( 2-methylpropyl ldiphosphonate A mixture of 2.0g of in 24g of trimethyl orthoformate is warmed at reflux for 18 hr. Low boilers are removed by fractionation through a short column during the reflux period. The excess orthoformate is then distilled at reduced pressure, and the residue is diluted with ether, and this mixture is filtered to give 0.5g of solid. Recrystallization from acetone gives tetramethyl- [urylenedi(2-methy1propyl)]diphosphonate, a white solid: mp 182-184.5; P nmr (CDCl )27.7 ppm; H nmr 86.61 (d, 2, J 101-12, CHNH), 4.3 (four doublets, 2, 1 18Hz, 1 10Hz, J 41-12, PCH(CH)NH), 3.76 (d, 6,1 1 =10Hz), 3.73 (d, 6, JCHSOP 10Hz), 2.06 [m, 2, CH(CH 1.03 d, 12, .l 7H2, CH(CH ir (KBr) 2.84(w), 3.00(m), 3.37(m), 5.93(s), 6.37(s), 6.79(m), 7.72(m), 8.04(vs).

EXAMPLE -7 Diethy1d-( 3-phenylureido )benzylphosphonate A P nmr measurement indicates that there is only a slow reaction when a mixture of 0.30 mole of triethyl phosphite, 0.30 mole of phenylurea, and 0.33 mole of benzaldehyde in 150g of toluene is warmed at 95100 for 0.5 hr. Boron trifluoride etherate (0.05 mole) is then added dropwise, causing a temperature rise. The reaction mixture is warmed at 95-100 for 1 hr and then stripped to a pot temperature of l20/l0mm. The residue is diluted with ether, causing separation of a solid (75.7g, including additional fractions from the filtrate). Recrystallization of a portion from acetonitrile gives a white solid: mp 150151.5; P nmr (CDCl 23.1 ppm; H nmr 88.35 (s, 1, NHC6H5), 6.7-7.8 (m,

11, C H and CHNH), 5.6 (d of d, 1, J 22Hz, .I =10Hz, CHNH), 3.5-4.6 (m, 4, CIj Cl-l 1.25 (overlapping triplets, 6, CH C1 -l Anal. Calcd for C H N O P: C, 59.66; H, 6.40; N, 7.73; P. 8.55. Found: C, 59.60; H, 6.41; N, 7.65; P, 8.69.

When the above preparation is modified by using citral instead of benzaldehyde, the product is diethyl 1-(3- phenylureido)-3,7-dimethylocta-2,6-dienyl-1-phos- I phonate.

EXAMPLE 8 This example shows the preparation of a phosphinate compound, i.e., a compound having two P-C bonds. It also shows the use of a thiourea as a reactant. When equimolar quantities of bis(2-chloroethyl) methylphosphonite, p-chlorophenylacetaldehyde, and phenylthiourea are warmed at 1 10C for 1 hour, 2- chloroethyl 1-(3-phenylthioureido)-2-(p-chlorophenyl) ethyl]methylphosphinate is formed. Hydrolysis gives the corresponding phosphinic acid.

This example shows the preparation of a phosphine oxide, that is a compound containing three P-C bonds. Warming (50100C) of a mixture of ethyl dimethylphosphinite, acetaldehyde and urea in the presence of a catalytic amount of boron trifluoride etherate gives dimethyl(1-ureidoethyl)phosphine oxide, a product that cannot be hydrolyzed to an acid of phosphorus.

When the above preparation is modified by using methylurea instead of urea, the product is dimethyl[1-(3- methylureido) ethyl]phosphine oxide.

EXAMPLE 9 2-Ethyl-1-ureidohexylphosphonic acid This compound is prepared from urea, tris( 2-chloroethyl) phosphite, 2-ethylhexaldehyde, and water under conditions similar to those used for the preparation of l-ureidopropylphosphonic acid in Example 4. The product is obtained as a white solid: mp 206C dec; P

nmr (CD SOCD 23.2 ppm; H nmr 88.5 (broad, 4, HO and N5 6.2 (d, 1, J 8H2, NH), 4.3 (d of d,l, J 8 and 20Hz, PCH), 1.3 and 0.9 (m, 15); acidity 2.00 equiv/mole, pK 3.50, pK 9.08.

Anal. Calcd for C H O N P: C, 42.85; H, 8.39; N'. 11.1 1;P, 12.28. Found: C, 42.89; H, 8.29; N, l 1.09; P,

EXAMPLE 10 1-(3,3Diphenylureido)ethylphosphonic acid Freshly distilled acetaldehyde (0.22 mole) is added during 0.5 hr to a stirred solution of 0.1 mole each of 1,1-diphenylurea and triphenyl phosphite in 130g of benzene at 60C. The solution is warmed at reflux (6570 with a Dry Ice-cooled condenser) for 1.25 hr, giving a dark brown solution having a small P nmr peak at ]26.2 ppm for unreacted phosphite and a large product peak at 18.4 ppm (-1 areas). The reaction mixture is stripped to l30/3mm and the residue diluted with 200 ml of acetonitrile and g of H 0, and

this solution warmed at reflux for 3 hr. Solid that separates during warming is recrystallized from acetic acidwater to give the product as a white solid: mp 186- 187C dec; F nmr 21.6 ppm; H nmr 810.0 (s, 2, OH), 7.3 (m, 10, C H 5.4 (d ofd, l, J =9 and 5H2, NH), 4.] (m, 1, CH), 1.3 (d of d, 3, .1 =16 and 7 Hz, CH acidity 2.00 equiv/mole, pK 2.20, pK 8.62. Anal. Calcd for C H N O P: C, 56.25; H, 5.35; N, 8.75; P, 9.67. Found: C, 56.43; H, 5.36; N, 8.84; P,

EXAMPLE 1 l Pre-emergent herbicidal activity of representative compounds of this invention is determined by the following procedure:

A good grade of top soil is placed in aluminum pans and compacted to a depth of three-eighths to one-half inch from the top of the pan. A pre-determined number of seeds of each of several plant species are placed on top of the soil in the pans. The seeds are covered with soil and the pans leveled. The herbicidal composition is applied by spraying the surface of the top layer of soil with a solution containing a sufficient amount of active ingredient to obtain a rate of application of 10 lbs. per acre. The pans are then placed on a sand bench in the greenhouse and watered from below as needed. The plants are observed at the end of approximately 14 days and the results recorded.

Pre-emergent activity of the compounds prepared in the designated examples is observed against the species as shown in the table below, wherein X denotes that herbicidal activity is observed.

continued PRE-EMERGENT TESTING Compound of Example 1 2 9 l0 Nutsedge X X Quackgrass X Johnsongrass X X X The nitrogen-containing organophosphorus compounds of the present invention are useful as fireretardants and as biological toxicants. The following examples illustrate the use of typical products.

A preliminary fire-retardant test is conducted as follows:

A 2 X 8 strip of cotton cloth is padded with a solution of equal parts of the test compound and 37% formalin, and the strip is dried at 65C and then cured at C for 0.5 hr. This is followed by washing with water and I then with acetone and drying to constant weight. This treated sample is applied to a Bunsen burner and then removed from the combustion zone of the burner after 5 seconds exposure to the flame. A sample which is self-extinguishing after this treatment is considered to pass the test. When tetrakis (2-chloroethyl) (ureylenediethyl)diphosphonate is used, and the addon is about 15%, the sample passes the test. Other rep- Loading Wt.% Time Required 0% 4.2 sec. 5% 10.1 7.5% 14.0 10% 17.6 for 2 samples (3 samples would not ignite) The above test is used with tetrakis(2 -chloroethyl) (urylenediethyl)-diphosphonate as the test chemical.

Compounds of this invention that contain at least ten percent halogen (especially chlorine and bromine) are particularly useful as fire-retardants.

Those that contain less than 10 percent halogen are also useful as synergists in enhancing the fire-retardance of halogen-containing polymers. For example, the fire retardant property of polyvinyl chloride is improved by use of materials of this invention, which provide the advantage of introducing phosphorus, for example in the proportion of about 1% to 10% by weight of the polyvinyl chloride. Compounds useful for this purpose include diethyl a-(3-phenylureido)benzylphosphonate, and dimethyl[(1-ureido)ethyl]phosphine oxide, and dimethyl[l-(3-methylureido)ethy11phosphine oxide.

9 10 What is claimed is: where 1. R' is alkyl of one to carbon atoms.

2. l-Ureidopropylphosphonic acid. 0 0 3. 2-Ethyl-l-ureidohexylphosphonic acid.

4. [Urylenedi(Z-methylpropyl)ldiphosphonic acid. ("0)2PCHNHCNH2 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION PATENT NO. 3,920,733

DATED Nov. 18, 1975 v 0 5 Gail H. Bi-rum It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

-- ROPR' H NZNR" R"CHO [SEAL] A ttesr:

RUTH C. MASON Attesting Officer equation Signed and Sealed this nineteenth Day of July 1977 C. MARSHALL DANN Commissioner of Patents and Trademarks 

1.FIG-01 WHERE R"'' IS ALKYL OF ONE TO 15 CARBON ATOMS.
 2. 1-Ureidopropylphosphonic acid.
 3. 2-Ethyl-1-ureidohexylphosphonic acid.
 4. (Urylenedi(2-methylpropyl))diphosphonic acid. 